Tislelizumab Monotherapy or Combined With Lenvatinib as Neoadjuvant Therapy for Resectable Hepatocellular Carcinoma.

NCT05807776 | Completed Phase 2

• 1 other identifier: 2211001174
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase II prospective study to evaluate the safety and efficacy of Tislelizumab monotherapy or combined with lenvatinib as neoadjuvant therapy for resectable hepatocellular carcinoma.

Conditions

Resectable Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• MPR rate

  tumor necrosis rate ≥ 50%

  4 months

Secondary Outcomes (6)

• 1-year and 2-years DFS%

  36 months

• ORR

  3 months

• Surgery delay rate

  3 months

• MiVI rate

  3 months

• mOS

  5 years

Study Arms (2)

tislelizumab

EXPERIMENTAL

Received tislelizumab for 2 cycles, 200mg, iv, d1,Q3W. Patients achieved PR or non-enlarged SD were enrolled in arm 1 and accepted surgery. After surgery, patients in arm 1 would receive tislelizumab as adjuvant therapy for 3-6 months.

Drug: Tislelizumab

tislelizumab+lenvatinib

EXPERIMENTAL

Received tislelizumab for 2 cycles, 200mg, iv, d1,Q3W. Patients achieved PD or enlarged SD were enrolled in arm 2 and continued to accept treatment with tislelizumab and lenvatinib for 2 cycles. After 2 cycles, patients would receive surgery according to their physical conditions. After surgery, patients in arm 2 would receive tislelizumab and lenvatinib as adjuvant therapy for 3-6 months.

Drug: Tislelizumab; Drug: Tislelizumab, Lenvatinib

Interventions

Tislelizumab DRUG

Tislelizumab 200mg, iv, d1, Q3W

tislelizumab; tislelizumab+lenvatinib

Tislelizumab, Lenvatinib DRUG

Tislelizumab combined with lenvatinib: Tislelizumab 200mg, iv, d1, Q3W Lenvatinib 8mg，po，qd.

tislelizumab+lenvatinib

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a known diagnosis of HCC as defined in the protocol
• Patients must be evaluated by the Department of Hepatobiliary Oncology, Tianjin Medical University Cancer Hospital to determine whether they can complete surgical treatment. Patients can be resectable in both oncology and surgery.
• At least ≥1 measurable lesion (RECIST 1.1)
• Age 18-75, male or female
• ECOG PS 0-1
• Child-pugh A
• The function of vital organs meets the following requirements (excluding the use of any blood component and cell growth factor within 14 days)
• Blood routine:
• Neutrophils ≥1.5×109//L Platelet count ≥100×109/L Hemoglobin ≥90g/L
• Liver and kidney function:
• Serum creatinine (SCr) ≤ 1.5 times upper limit of normal value (ULN) or creatinine clearance ≥50 ml/min (Cockcroft-Gault formula) Total bilirubin (TBIL)≤ 1.5 times the upper limit of normal value (ULN) AST or ALT levels ≤ 3 times the upper limit of normal value (ULN)
• Normal coagulation function, International standardized ratio INR≤1.5×ULN or Prothrombin time PT≤1.5ULN
• Normal thyroid function is defined as thyroid stimulating hormone (TSH) within the normal range. Subjects whose baseline TSH is outside the normal range may be enrolled if total T3 (or FT3) and FT4 are within the normal range.
• Myocardial enzyme profiles were within the normal range (simple laboratory abnormalities that were not clinically significant were also allowed to be included)
• Patients who have progressed to PD or increased SD after 2 cycles of tislelizumab monotherapy must be willing to continue 2 cycles of tislelizumab and Lenvatinib combination therapy and be evaluated.

You may not qualify if:

• Have received any systemic anticancer therapy or radiotherapy for their current tumor or other primary tumor in the 6 months prior to study entry.
• Tumor load or tumor growth rate was considered by the investigator to be insufficient to delay surgery.
• Had major surgery within 14 days prior to neoadjuvant therapy.
• Uncontrolled co-morbidities defined in the protocol and identified by the investigator.
• Receiving systemic steroid therapy or any other immunosuppressive therapy within 7 days prior to administration of the first dose of study therapy.
• Have had an active autoimmune disease requiring systemic treatment within the past 1 year.
• Have other malignancies that are known, developing and/or require aggressive treatment.
• Informed consent to encephalitis, meningitis, or uncontrolled seizures in the previous year.
• A history of interstitial lung disease (e.g., idiopathic pulmonary fibrosis, systemic pneumonia) or active non-infectious pneumonia requires immunosuppressive doses of glucocorticoids to assist in treatment.
• Bleeding from esophageal or fundus varices caused by portal hypertension in the past 6 months; Severe (G3) varicose veins were known on endoscopy within 3 months prior to initial administration; Patients with evidence of portal hypertension (including imaging findings of a large spleen diameter of more than 10cm and platelets of less than 100) were at high risk of bleeding as assessed by the investigators.
• History of arteriovenous thromboembolism events within the past 6 months, including myocardial infarction, unstable angina pectoris, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or any other severe thromboembolism. Implantable venous port or catheter-derived thrombosis, or superficial venous thrombosis, except in patients with stable thrombus after conventional anticoagulant therapy.
• Severe bleeding tendency or coagulopathy, or receiving thrombolytic therapy.
• Prophylactic use of low-dose, low-molecular heparin (e.g., enoxaparin 40 mg/ day) is permitted, except for vitamin K antagonists (e.g., warfarin).
• Long-term use of drugs that inhibit platelet function such as aspirin, dipyridamole or clopidogrel is required.
• Uncontrolled hypertension, systolic blood pressure \> 140mmHg or diastolic blood pressure \> 90 mmHg after optimal medical treatment, history of hypertensive crisis or hypertensive encephalopathy.

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

Study Sites (1)

Tianjin Medical University Cancer Institute & Hospital

Tianjin, Tianjin Municipality, 300060, China

Location

MeSH Terms

Interventions

tislelizumab; lenvatinib

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2023
• First Posted: April 11, 2023
• Study Start: April 24, 2023
• Primary Completion: July 24, 2024
• Study Completion: July 31, 2025
• Last Updated: April 1, 2026

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)